Mechanical abusive loadings, as an inevitable consequence of road accidents, can damage the embedded energy storage system in an electric vehicle and deform its constitutive parts, e.g., the lithium-ion batteries. Therefore, to study the mechanical responses of these batteries and avoid expensive testing equipment and rigorous safety percussions, researchers are propelled toward utilizing numerical models. Computationally cost-efficient homogenized finite element models that represent the whole battery in the form of a uniform medium are the most feasible solution, especially in large-scale battery stacks simulations. Compared to the other form factors of the batteries, prismatic cells have been understudied even though they have higher packaging efficiency, by making optimal use of space. In this article, a comprehensive homogenization and failure calibration method was developed for these prismatic cells. The homogenization was done through extensive uniaxial components tests of the jellyroll and the shell casing. In addition, biaxial tensile tests and simulations were used to calibrate strain-based failure criteria for the components. The calibrated homogenized model is validated in various punch loading scenarios and used in the characterization of the load–displacement responses and failure modes of the stacked cell configurations. In the stacked simulations, due to the cushion-like behavior of the other cells, the failure happens in higher values of displacement compared to a single cell. However, the normalized intrusion percentages for the battery stacks are lower compared to a single battery cell. This emphasizes the importance of the safety assessment of an electric vehicle based on the failure analysis of the battery stacks rather than a single cell. This goal would be feasible through simulations of only homogenized cell models in the stacked configurations, which are elaborated in this article for prismatic cells.